Phenyl nu-alkyl thiolcarbamate microbiocide



United States Patent 3,265,563 PHENYL N-ALKYL THIOLCARBAMATEMICROBIOCIDE Harry Tilles, El Cerrito, and Thomas B. Williamson,

Santa Clara, Calif., assignors to Stauifer Chemical Company, New York,N.Y., a corporation of Delaware No Drawing. Original application May 1,1961, Ser.

No. 106,445. Divided and this application Oct. 21,

1963, Ser. No. 320,245

10 Claims. (Cl. 167-30) This application is a division of applicationSerial No. 106,445, filed May 1, 1961, now abandoned.

This invention relates to the use of such compounds as microbiocides.

More specifically, the invention relates to compounds of the formula:

wherein R is a lower alkyl group and X is hydrogen or chlorine.

The compounds of the present invention have been tested and areparticularly useful as bactericides and fungicides.

The following illustrative examples demonstrate the methods which may beemployed to make typical com pounds of the present invention.

Example I.C0mpound 6: p-Chlorophenyl N-efhylthiolcarbamate A l. 3 neckflask was provided with stirrer, thermometer and addition funnel. 538 g.(2.60 moles) of pchlorophenyl chlorothiolformate, 1000 cc. of ethylether and 1250 cc. of water were charged to the flask and the mixturewas cooled to 2 C. 342 g. (5.33 moles) of 70% aqueous ethylaminesolution was then carefully added, maintaining the temperature between1.5-3.5 C. with external cooling. After completion of the addition, themixture was stirred for an additional 48 minutes at 3-9" C. It was thentransferred to a 4 l. beaker and the mixture was heated to 58 C. on thesteam bath in order to remove the ether. The solid was then filtered andreslurried in 2 l. of water. It was then filtered and dried.

The crude product, M.P. 98.5-l08 C., wt.=526 g., was recrystallizedtwice from isoheptane. There was obtained 433 g. (77.0% yield) ofp-chlorophenyl N- ethylthiolcarbamate, M.P. 109.5111.5 C.

Analysis.Calculated for C H CINOS: N, 6.49%; CI, 16.44%. Found: N,6.26%; CI, 16.44%.

Example II.C0mp0und 7: p Chlor-ophenyl N-n-propylthiolcarbwmate When thegeneral procedure of Example I was repeated except that 327 g. (5.54moles) of n-propylamine, 560 g. (2.70 moles) of p-chlorophenylchlorothiolformate, 1000 cc. of ethyl ether and 1250 cc. of water wereemployed, there was obtained 515 g. (83.1% yield) of p-chlorophenylN-n-propylthiolcarbamate, M.P. 96.0-'

Analysis.Calculated for C H ClNOS: N, 6.10%; Cl, 15.43%. Found: N, 6.0%;Cl, 15.2%.

Example III.'C0mp0und 8: p-Chlorophenyl N-n-butylthiolcarbamateAnalysis.Calculated for C H ClNOS: N, 5.75%; Cl, 14.55%. Found: N, 5.9%;Cl, 14.4%.

Example I V.Comp0und 5: p-Chlorophenyl N-allyltlzz'olcarbamate 10 g.(0.048 mole) of p-chlorophenyl chlorothiolformate was dissolved in 125cc. of ethyl ether and cooled in an ice bath. 5.6 g. (0.099 mole) ofallylamine was then slowly added with cooling. A precipitate ofallylamine hydrochloride formed immediately. The solid was filtered andthe filtrate was concentrated on the steam bath. There remained behind,8.3 g. (75.5% yield) of p-chlorophenyl N-allylthiolcarbamate, M.P.109.51l2.5 C.

Example V.C0mpormd 2: Phenyl N- e-thylthiolcarbamate 7.7 g. (0.119 mole)of 70% ethylamine solution, 50 cc. of ethyl ether and 50 cc. of waterwere added to a 3-neck 200 cc. flask provided with stirrerandthermometer and the mixture was cooled to 5 C. 10 g. (0.058 mole) ofphenyl chlorothiolforrnate was then added slowly with cooling. After theaddition was completed, the ether layer was then separated from theaqueous layer and washed with 1-50 cc. portion of water. It was thendried over anhydrous magnesium sulfate and evaporated on the steam bath.There remained behind, 6.4 g. (61% yield) of phenylN-ethylthiolcarbarnate, M.P. 69.0-76.0 C.

Example VI.C0mp0und 3: Phenyl N-npropylthiolcarbamate When the generalprocedure of Example IV was repeated except that 7.0 g. (0.119 mole) ofn-propylamine, 10 g. (0.058 mole) of phenyl chlorothiolformate and 125cc. of ethyl ether were employed, there was obtained 10.3 g. (91.1%yield) of phenyl N-n-propylthiolcarbamate, M.P. 70.575.0 C.

Example VIl.C0mp0und 4: Phenyl N-n-butylthiolcarbamate When the generalprocedure of Example IV was repeated except that 8.7 g. (0.119 mole) ofn-butylamine, 10 g. (0.058 mole) of phenyl chlorothiolformate and 125cc. of ethyl ether were employed, there was obtained 11.9 g. yield) ofphenyl N-n-butylthiolcarbamate, 11 1.5547.

Example VIII.-C0mp0und 1: Phenyl N-allylthiolcarbamate When the generalprocedure of Example IV was repeated except that 6.8 g. (0.119 mole) ofallyl-amine, 10 g. (0.058 mole) of phenyl chlorothiolformate and cc. ofethyl ether were employed, there was obtained 11.1 g. (99.2% yield) ofphenyl N-a1lylthiolcarbamate, 11 1.5828.

The compounds of the present invention were used in various tests whichwill hereinafter be described.

In vitro test.This test measures the fungicidal and bactericidalproperties of the compounds being tested when in contact with a growingfungus or bacterium in an artificial medium.

The compounds to be tested are each placed in a vial of malt broth atvarious rates expressed in parts per million. Next, water suspensions ofspores of Aspergillus niger, Sclerotinia fructicola, and Stemphylium Sp.are added to the vials to test the fungicidal activity of thecompounds.'

Cells of Staphylococcus aurcus, Erwinia amylovora, and Escherichia coliare added (one organism per vial) to test bactericidal activity. Oneweek later the results are read.

Agar plate fumigation test.-This test indicates whether or not acompound has a fungicidal vapor phase.

Approximately 0.1 gram of compound is placed in a 0.5 ml. microbeaker ina Petri dish of hardened potato dextrose agar. Aspergillus niger sporesare dusted onto the agar and the dish is closed. One week later, growthof the fungus is recorded as percent control.

Foliage fungicide test.This test indicates protectant action as well aseradicant and leaf systemic action against fungi attacking plantfoliage.

Pinto bean plants are thoroughly sprayed with three concentrations ofdissolved or suspended chemical in water. After drying, the plants areinoculated with rust or powdery mildew spores. Results are read Whendisease symptoms are distinct on untreated beans and reported in percentcontrol. Northern corn was also treated in the same manner and infectedwith leaf blight.

Nematocide soil incorporation test.This test determines a chemicalsaction on nematodes in the soil.

Soil is infested with root-knot nematodes and then treated with the testcompounds. After leaving the soil sealed for 48 hours, tomatoes areplanted as the indicator plant after allowing the soil to air out. Thenematodes, if they survive, attack the roots and cause swellings orknots. These are observed four weeks after treatment.

The following table shows the results of the tests de- 6. The method asstated in claim 3 wherein X is hydrogen.

7. The method as stated in claim 4 wherein X is hydrogen.

8. The method as stated in claim 2 wherein X is chlorine.

9. The method as stated in claim 3 wherein X is chlorine.

10. The method as stated in claim 4 wherein X is chloscribcd supra.rine.

IN VI'IRO TESTS (Bacteria) Compound R X Aspergillus Sclerotim'aStemphylium Percent No. niger fructicola sp. Agar Fum.,

S. uureus E. amylovora E. coli 50 (100) 25 25 50 95 50 50 (100) 25 25 2520 50 50 (100) 25 25 50 0 50 50 100) 25 25 25 90 (100) 50 500 0 (50) 50100 10 10 10 0 50 50 500 10 5 l0 O n-Butyl 50 50 (100) 10 5 5 0 Numbersin vitro tests=complete control at that concentration in ppm.Parentheses indicate partial control at indicated rate.

FOLIAR TESTS Bean Rust Bean Mildew N 0. Corn Leaf Bl. Root Compound R XKnot No. Nemas 75 0 0 d 0 d 0 0 0 0 0 0 0 0 0 0 d 0 0 0 d 0 0 0 0 d 90 00 d 50 d 0 0 0 100 100 75 90 75 50 90 90 0 0 M00 90 0 90 90 0 50 50 0(110) d 100 90 0 100 90 50 90 75 0 0 n-BntyL. d 100 90 0 75 50 90 0 75 0(110) =s1ight phytotoxicity. =moderate phytotoxicity. Parenthesesindicate partial control at indicated rate.

As described in the examples herei-nbefore given, the References Citedby the Examiner method for making the compounds of the present mven-UNITED STATES PATENTS tion involves a substitution reaction in which alower alkyl group of an alkyl amine is substituted for the 2,977,209 3/1961 Tllles 260-455 chlorine atom of a phenyl chlorothiolformate. Thisre- 2,990,319 6/1961 Jones 16730 action is carried out in the presenceof ethyl ether or 3,098,001 7/ 1963 WeTfeS 16730 equivalent solvents.FOREIGN PATENTS Throughout the specification, the term lower alkyl groupis meant to include an allyl group although strictly 961,042 3/1957Germany speaking it is an alkylene group. OTHER REFERENCES We claim:v 1. The method of controlling microorganisms compris- ChemlcalAbstracts 55: 14822(c) (1961) abstractmg ing contacting the pest habitatwith a compound of the following formula:

Arch. Pharm. (Berl), vol. 294, No. 66,'pp. 201 to 209, April 1961.

JULIAN S. LEVITT, Primary Examiner.

' J. D. GOLDBERG, Assistant Examiner. A Q

1. THE METHOD OF CONTROLLING MICROORGAANISMS COMPRISING CONTACTING THEPEST HABITAT WITH A COMPOUND OF THE FOLLOWING FORMULA: